Chiral ferrocenyldiphosphines have proven to be valuable ligands for catalytically active metal complexes which are used in homogeneous catalysis for the enantioselective hydrogenation of organic compounds. Fields of use are the preparation of intermediates or active compounds, for example pharmaceuticals, pesticides, flavors or fragrances.
Among the diphosphines having a ferrocene framework, 1-sec-phosphino-2-(2′-sec-phosphino-1-benzyl)-ferrocenes, for example, have proven to be valuable ligands for noble metal complexes for the enantioselective hydrogenation of organic compounds. Ligands of this type are referred to by the name “Taniaphos” and are described in WO 00/37478. Further examples of diphosphines having a ferrocene framework are 1-(α-sec-phosphinoalkyl)-2-(sec-phosphinoaryl)-ferrocenes which are disclosed in WO 02/02578 (trivial name “Walphos”).
In enantioselective hydrogenation, these diphosphine ligands are used together with suitable noble metal complexes. The reaction of asymmetric ferrocenyldiphosphine ligands with organometallic Ru compounds leads to mixtures of complexes which have monodentate coordination of the P atoms of the phosphine ligand, cf. equ. (1):
According to equ. (1), an isomer mixture of monodentate, P-coordinated Ru complexes in which in each case, only one of the P atoms of the ferrocenyldiphosphine ligand is bound to the ruthenium is present. The two isomers in equation (1) can be distinguished, for example, by means of 31P-NMR spectroscopy. Simultaneous coordination of both P atoms of the ferrocenyldiphosphine ligand in a ruthenium complex (hereinafter referred to as “bidentate” coordination or “P—P coordination”) has hitherto not been observed.
Organometallic Ru compounds used in these hydrogenations are, for example, [Ru(COD)Y2]x, [Ru(NBD)Y2]x, [Ru(aromatic)Y2]x or [Ru(COD)(2-methylallyl)2] (where X=2; Y=halide, COD=1,5-cyclooctadiene, NBD=norbornadiene, aromatic=for example, p-cumene or another benzene derivative).
EP 1622920B1 discloses transition metal complexes with ferrocenyldiphosphine ligands. Complexes having specific P—P coordination of the phosphine ligands are not described, and in addition the diphosphine ligands disclosed have phosphine groups which are located on different ferrocene rings of the ligand system.
Although WO 00/37478 describes transition metal complexes which contain a metal atom of transition group 7 or 8 and in which both P atoms of the ferrocenyldiphosphine ligand are simultaneously coordinated to the central atom, the complexes are neither isolated nor characterized. No process for preparing them is described; rather, the complexes are generated shortly before use by combining the ligands and the appropriate transition metal salts in the reaction solvent (“in situ”).
These in-situ processes are prior art. Thus, ferrocenyldiphosphine ligands are reacted with ruthenium complexes in an in-situ procedure; cf. Angewandte Chemie 1999, 111, No. 21, 3397-3400. Here, [Ru(COD)(C4H7)2]HBr (COD=cycloocta-1,5-diene, C4H7=2-(η3-)methylallyl) is used as Ru complex and β-keto esters of the type R—CO—CH2—CO—OEt are hydrogenated in ethanol at 50° C. under 50 bar of hydrogen. The same Ru starting compound is used in Tetrahedron Asymmetry 15 (2004) 91-102 and the catalyst is prepared in situ.
Adv. Synth. Catal. 2003, 345, 160-164 describes phenyl-ferrocenylethyldiphosphine ligands of the “Walphos” type. Dimeric [RuI2(p-cumene)]2 is used as Ru-containing catalyst precursor in the hydrogenation and the catalyst is formed in situ.
However, no studies on the structure of the metal complexes generated in situ have hitherto been carried out; the corresponding complexes were not isolated but used directly in the reaction mixture for homogeneous catalysis, in particular for catalytic hydrogenation.
Disadvantages of the catalytic hydrogenation processes which have been described up to now and the catalysts used therein are, in particular, the low enantio-selectivities and a high consumption of noble metal catalysts, i.e. a low substrate/catalyst (S/C) ratio, and long hydrogenation times.